title: Effects of des-aspartate-angiotensin I on myocardial ischemia-reperfusion injury in rats.
abstract: The present study investigated the actions of des-aspartate-angiotensin I (DAA-I) on infarct size and three early inflammatory events in acute myocardial ischemia-reperfusion injury in rats. The rationale was based on earlier findings showing that chronic daily administration of DAA-I attenuated infarct size of ischemic-reperfused rat heart, and cardiac hypertrophy in pressure overload rats. Anesthetized rats were subjected to 45 min of ischemia and 5h of reperfusion. Infarcted area, serum creatine kinase, and tissue myeloperoxidase activity were determined. The expression of intercellular adhesion molecule-1 (ICAM-1) was also investigated by immunohistochemistry and Western blotting. Intravenous administration of DAA-I at 5 min post reperfusion reduced myocardial infarct size by 45.5%, lowered serum creatine kinase activity, decreased myeloperoxidase activity in cardiac tissue, and inhibited the expression of ICAM-1 in cardiac capillary endothelium. The maximum effective dose was 1013 pmol/kg, and the cardioprotective actions of DAA-I were blocked by indomethacin. The data showed that the cardioprotection accorded by DAA-I was the result of its anti-inflammatory actions on early inflammatory processes in myocardial ischemia-reperfusion injury. The anti-inflammatory processes were indomethacin sensitive and probably mediated by prostaglandins.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wen
authors.forename: Meng-Kwoon
authors.initials: MK
authors.lastname: Sim
mesh_terms: D000803:Angiotensin I / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D003402:Creatine Kinase / Q000097:blood; D005786:Gene Expression Regulation / Q000187:drug effects; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D017202:Myocardial Ischemia / Q000150:complications*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: C529402:des-aspartate-angiotensin I; D018799:Intercellular Adhesion Molecule-1; D000803:Angiotensin I; D009195:Peroxidase; D003402:Creatine Kinase